Altered sensory processing is a common feature of autism spectrum disorders (ASD). Although defective sensory circuitry in the brain is believed to underline abnormal somatosensation in ASD, a contribution of peripheral circuitry has been recently identified. Neurotrophin/trk signaling controls multiple aspects of somatosensory neurodevelopment, and phosphatase and tensin homolog (Pten), a known ASD susceptibility gene, functions as a key negative regulator of this pathway. However, it remains to be determined how loss of Pten affects primary sensory neuron survival, population diversity and circuit formation and function. My preliminary data suggest that survival, cell-fate determination, differentiation, and target innervation are disrupted in primary sensory neurons in Pten mutants. I will now test the hypothesis that altered Pten signaling in primary sensory neurons compromises peripheral nervous system circuit development, ultimately leading to altered sensory processing. There are several distinct mechanisms by which Pten deletion may affect the development of peripheral sensory circuits: altered survival of peripheral sensory neurons, abnormal DRG subpopulation diversification, and altered neuronal morphology and innervation patterns. In Specific Aim 1, I will interrogate these cellular mechanisms and identify the molecular pathways that drive pathogenic changes during somatosensory development. In Specific Aim 2, I will define how loss of Pten alters innervation patterns of primary sensory neurons, and I will determine whether altered somatosensory neuron development and function, due to disrupted Pten signaling, contributes to sensory phenotypes. Altogether, this project will establish the relationship between specific cellular defects in the developing peripheral nervous system and altered circuit organization and function; offering fundamental insight into the mechanisms underlying a key clinical feature of ASD. My long-term goal to develop an independent line of research studying the contribution of abnormal circuit formation to the behavioral phenotypes in ASD. Thus, this K01 award will serve me to 1. develop my technical skills through the research plan, 2. acquire a strong foundation in quantitative analysis as well as in imaging techniques, through courses at the Cold Spring Harbor and in my home institution, and 3. interact and gather professional advice from senior scientists who serve as my co-mentors, in a collaborative environment that has a training program designed specifically to provide professional development to post-doctoral trainees. Thus, this award will serve me to acquire the methodological, intellectual and professional skills to conduct outstanding, quantitatively rigorous research in the future as an independent investigator.